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| Status |
Public on Oct 27, 2016 |
| Title |
Early whole blood transcriptional signatures are associated with severity of lung inflammation in cynomolgus macaques with Mycobacterium tuberculosis infection |
| Platform organism |
Homo sapiens |
| Sample organism |
Macaca fascicularis |
| Experiment type |
Expression profiling by array
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| Summary |
This longitudinal dataset was generated to assess changes in whole blood gene expression following low dose Mycobacterium tuberculosis infection of Cynomolgus macaques. In addition to changes in mRNA transcript abundance, changes in circulating immune cell populations were also assessed using both complete blood counts (CBC) and using flow cytometry. Disease severity was determined using both clinical diagnosis (active vs. latent) and 18F-flurodeoxyglucose (FDG avidity) by 6 months post-infection. The greatest change in transcriptional activity occurred 20-56 days after infection, when the maximum activity of immune related transcripts was observed. After stratifying macaques based on clinical diagnosis, those macaques with active disease exhibited a similar signature to that observed in humans with active TB. However, only modest transcriptional differences between active TB and latently infected macaques were observed. As an alternative stratification approach, the severity of lung inflammation measured by lung FDG avidity was used to separate macaques into high and low FDG groups. Blood transcript activity was highly correlated with lung inflammation at early time points post-infection. The differential expression signatures between animals stratified with high and low lung FDG were stronger than those observed with groups defined by clinical outcome.. Furthermore, gene level analysis of of pre-infection signatures suggest that interferon and inflammation signatures may distinguish eventual clinical outcomes and lung FDG avidity prior infection. In conclusion, this study demonstrates that transcriptional changes in the macaque model recapitulate those observed in human Mtb infection while providing additional insight into the early and pre-infection events associated with disease severity and outcome.
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| Overall design |
In total, the responses of 38 Cynomolgus macaques to low dose Mtb infection (Erdman ~25CFU) were assessed in this study. Blood draws for the assessment of gene expression and cellular composition were assessed at two time points prior to infection (Pre1 and Pre2) and at days: 3,7,10,20,30,42,56,90,120,150,180 post-infection. Binary clinical diagnosis (active v. latent) and lung inflamation (FDG avidity) were both used used to stratify the severity of infection outcome. Those samples that were taken at the time of clinical diagnosis along with the pre-infection control are denoted by Yes in the SynchroSet column.
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| Contributor(s) |
Gideon HP, Skinner JA, Baldwin N, Flynn JL, Lin PL |
| Citation(s) |
27837110 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL106804 |
Defining how the spectrum of latency affects reactivation of TB |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
JoAnne L. Flynn, Denise E Kirschner |
| R01 AI111871 |
HIV-TB Co-infection: Tracking TB emergence after asymptomatic (latent) infection |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
Philana Ling Lin |
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| Submission date |
Jul 07, 2016 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Jason A Skinner |
| E-mail(s) |
[email protected]
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| Organization name |
Baylor Institute for Immunology Research
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| Street address |
3434 Live Oak
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75204 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (470)
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| Relations |
| BioProject |
PRJNA328153 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84152_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE84152_non-normalized.txt.gz |
132.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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